Host resistance to cancer almost certainly involves multiple immunospecific and non-specific mechanisms. Compelling in vitro evidence suggests an innate system of resistance involving macrophages and natural killer cell cells and emerging tumors provoke immune responses. Accordingly, the proposed experiments address a crucial issue: how do malignant cells in vivo evade destruction. The experimental approach will be to examine the significance and causation of tumor related anti-inflammation. We have determined that tumor bearing produces a biphasic depression in macrophages responses. The first phase arises concurrently with tumor transplantation and is transient. The second phase begins mid-way in the clinical course and persists until death from cancer. We are in the process of examining the factors responsible for the early and late phases of inhibition. In addition, we are examining various models of spontaneously arising neoplasms to determine if they behave similarly to transplanted tumors.